US7586089B2 - Feedback fragmentation in ion trap mass spectrometers - Google Patents

Feedback fragmentation in ion trap mass spectrometers Download PDF

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US7586089B2
US7586089B2 US11/610,569 US61056906A US7586089B2 US 7586089 B2 US7586089 B2 US 7586089B2 US 61056906 A US61056906 A US 61056906A US 7586089 B2 US7586089 B2 US 7586089B2
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US20070158544A1 (en
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Ralf Hartmer
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Bruker Daltonics GmbH and Co KG
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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0027—Methods for using particle spectrometers
    • H01J49/0031—Step by step routines describing the use of the apparatus
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0045—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn characterised by the fragmentation or other specific reaction
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H01J49/0081—Tandem in time, i.e. using a single spectrometer
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/26—Mass spectrometers or separator tubes
    • H01J49/34—Dynamic spectrometers
    • H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons

Definitions

  • the invention relates to acquisition methods for fragment ion spectra of peptides in RF ion trap mass spectrometers, which are usually coupled to separation methods such as chromatography or capillary electrophoresis.
  • Tandem mass spectrometers comprise a first mass spectrometer to select ions of a certain type, a fragmentation device, in which these selected ions are fragmented, and a second mass spectrometer to analyze the fragment ions.
  • these processes of selecting, fragmenting and analyzing the fragment ions can also be performed in temporal succession within the same ion trap; this is then termed “tandem-in-time”, in contrast to “tandem-in-space” in the case of spatially separated mass spectrometers.
  • a Paul ion trap generally consists of a ring electrode and two end cap electrodes.
  • An RF voltage at the ring electrode generates a quadrupole RF alternating field in the interior, which drives ions back into the center regardless of their polarity. Without collision gas, the ions oscillate in the ion trap in this so called pseudopotential well. The frequency of these so called “secular” oscillations is strongly characteristic for the charge related mass m/z of the ions.
  • the ion trap is normally filled with a collision gas, usually helium, at a pressure of some 10 ⁇ 2 Pascal, so that the oscillation is damped in a few milliseconds by a large number of gentle collisions and the ions arrive in relative calm in the center of the ion trap, forming a small cloud.
  • the energetic states in the interior of the molecules are also reduced; this is termed “cooling” by the collision gas.
  • the diameter of the ion cloud in the center of the ion trap is determined by the equilibrium between the centripetal force of the RF field and the centrifugal force of the Coulomb repulsion between the ions.
  • the ions can be excited to swinging secular oscillations by a dipolar excitation alternating voltage across both end cap electrodes, particularly when the excitation frequency matches the secular oscillation frequency. This is termed “resonant excitation”.
  • the ions can be selectively ejected from the ion trap according to their mass by several known methods and can thus be measured in an ion detector as a mass spectrum.
  • all ion species of an ion source are first stored; the ion species which are not to be analyzed are then ejected using known methods so that only the ion species to be analyzed as “parent ions” remains in the ion trap. This process is termed “isolation” of the selected parent ions.
  • These parent ions can now be fragmented, for example by forced collisions with the collision gas under continuous resonant excitation.
  • the fragments which remain behind as ions can then be selectively ejected according to their mass and measured as a fragment ion spectrum.
  • the fragment ion spectrum is also termed “daughter ion spectrum”.
  • ion trap which is usually called a “three-dimensional ion trap”
  • linear ion trap which comprises four pole rods with end electrodes resembling apertured diaphragms.
  • the manner of operation of this linear ion trap will not be discussed here. It must be incorporated into the basic idea of the invention, however, since the idea is not dependent on the type of ion trap, as long as this ion trap has quadrupole RF alternating fields and means for collisionally induced fragmentation.
  • ion trap mass spectrometers are usually equipped with electrospray ion sources, which supply not only singly charged ions of the digest peptides but also doubly and triply charged ions, which are particularly suitable for fragmentation with a high information content.
  • CID collisionally induced fragmentation
  • EID electron induced fragmentation
  • CID and EID contain complementary information, and so are preferably applied to the same ion species, preferably even to ions of different charge states of this ion species.
  • a characteristic feature of collisionally induced fragmentation CID is that longer or heavier modifying side chains, for example phosphorylation, sulfate or glycosylation groups, are preferably split off from the chain of the amino acids as neutral fragments because, generally, they are bound with low binding energy.
  • the fragment ion spectrum hence reflects only the naked chain of the amino acids, not their modifications. The knowledge concerning the modification is lost completely if their splitting off does not leave behind changes to the amino acids themselves. This is the case in rare cases only, such as the creation of dehydroxyserine when serine is dephosphorylated.
  • b fragment ions if the N-terminal fragment remains as an ion charged with a proton, otherwise as a y fragment ion for the C-terminal fragment ion. If one starts with doubly charged ions, then it is frequently the case that both ions of the complementary b and y fragment ion pair occur.
  • the y ions are always 16 atomic mass units heavier than the z ions.
  • unusual masses for the mass separations between the ion signals in the EID spectrum immediately make it apparent which of the amino acids carries the modification and what mass this modification has. It is thus favorable to measure both the CID and the EID fragment ion spectrum for each peptide. If the time available does not allow this, then at least the EID fragment ion spectra for the modified peptide ions should be measured.
  • the upstream separation method for the biopolymers provides the mass spectrometer with the analyte substance, in this specific case a digest peptide, for only a few seconds.
  • analyte substance in this specific case a digest peptide
  • several digest peptides are often supplied simultaneously at any one time; not infrequently even between ten and twenty digest peptides simultaneously.
  • An ion trap mass spectrometer can acquire around three to five mass spectra per second, so the measurements must be carried out sparingly.
  • the control programs of this ion trap mass spectrometer contain methods to automatically acquire fragment mass spectra; they are briefly described here:
  • a continuous series of normal mass spectra are acquired.
  • the normal mass spectra are stored digitally in the memory of the mass spectrometer.
  • an evaluation program is then used to determine in real time whether one or more digest peptides are in fact supplied in sufficient concentration. If this is the case, a mathematical analysis of the mass spectrum is then used to select which ion species is most favorable for the acquisition of a fragment ion spectrum. Analyses of this type are familiar to those skilled in the art; in particular, it is known how singly, doubly and triply charged ion species can be identified using the mass separations in the isotope pattern.
  • Doubly or triply charged ions are best suited to collisionally induced fragmentation, so the most intensive ion species which occurs with a double or triple charge within a predetermined mass range, not listed in an exclusion table, is generally used for the acquisition of the next fragment ion spectrum.
  • the exclusion table contains the mass values of those peptides which have already been analyzed in previous measuring cycles or which were marked as not of interest at the outset.
  • the selected species of parent ion is then isolated in the ion trap and fragmented by resonant excitation in the next acquisition cycle; the fragment ions are then measured in the form of a fragment ion spectrum.
  • an EID fragment ion spectrum most favorably begins with triply or four times charged parent ions. If time allows, it is advisable to immediately measure both the CID as well as the EID fragment ion spectra for all the ion species which occur.
  • the modified peptides frequently do not provide good fragment spectra.
  • a modification group splits off from the peptide as a neutral fragment; the residual peptide is then no longer resonantly excited, but is quickly cooled in the collision gas; it can no longer decompose further under these conditions.
  • the fragment spectrum then essentially comprises only one single dominant ion species, which still carries the same number of charges as the parent ions, but has less mass.
  • Peptide ions which are complexed with alkali ions are also distinguished by the occurrence of a dominant ion species in the fragment ion spectrum, but the dominant ion species carries one charge less than the selected parent ions. The alkali ion is lost here.
  • the spectra of electron-induced fragmentation also often exhibit only one single dominant peak, generally a radical ion which does not independently decay any further, but carries a lower charge than the parent ions.
  • a rough rule of thumb is that around five to fifteen percent of all fragment ion spectra exhibit such a dominant ion signal.
  • the invention provides a method which analyzes each fragment ion spectrum in real time to see if it contains a dominant ion signal, and, when necessary, repeats the measurement on the same ion species, thereby improving the result by subjecting the ions of the dominant ion signal to an additional collisionally induced fragmentation by means of a resonant excitation.
  • the first mode of fragmentation used can be either a collisionally induced fragmentation or an electron-induced one.
  • the additional collisionally induced fragmentation in the repeat measurement can be generated by a method known as MS/MS/MS or MS 3 , with the ions of the dominant ion species also being subjected to an isolation; but it is more favorable and time-saving if, during the repeat measurement following the first fragmentation, this ion species is subjected to a second fragmentation by resonant excitation without further isolation.
  • the method can be repeated by fragmenting this new, dominant ion signal in order to also record the sequential splitting off of two modification groups. It is entirely possible that small numbers of triply phosphorylized peptides occur, so that a further step of this type can be useful. In general, however, these tests can be called off after the second repeat since, in this case, it is highly probable that it is not a peptide at all but an impurity.
  • Discretion can be exercised regarding the definition of what constitutes a “dominant ion species”. It can be an ion species whose intensity is more than twice that of the next most frequent ion species; it can also be an ion species whose frequency is more than ten times greater than all the other ion species together. It is advisable to keep these conditions adjustable so that they can be adapted to the analytical objective.
  • FIGS. 1A-1C illustrate three fragment ion spectra which were scanned in the automatic measurement of a triply charged modified peptide (amino acid sequence: IGRFSEPHAR). The amino acid serine at position 5 is phosphorylated.
  • FIG. 1A illustrates the daughter ion spectrum obtained by collisionally induced fragmentation; the collisionally induced fragmentation means that the neutral loss of H 3 PO 4 is particularly favored so that the residual peptide ion in the spectrum occurs as the dominant signal (identified with a “ ⁇ ”). According to this invention, the occurrence of this dominant ion signal leads to the automatic measurement of the spectra shown in FIGS. 1B and 1C .
  • FIG. 1B shows a fragment spectrum obtained from a collisionally induced fragmentation of the dominant ion signal without further isolation.
  • the fragment ion spectrum is still of only moderate quality but clearly better than the spectrum in FIG. 1A .
  • FIG. 1C illustrates a spectrum of the fragment ions produced by electron transfer dissociation, triggered and automatically scanned by the occurrence of the dominant ion signal in the spectrum of FIG. 1A .
  • the quality of this ETD fragment ion spectrum is excellent and it shows the complete sequence of the amino acids as c ions, all at an intensity of 10% to 20%, with the phosphorylation of the serine being preserved.
  • FIG. 2 is a flowchart showing the steps in an illustrative process operating in accordance with the principles of the invention.
  • the invention provides a method which uses the shape of the fragment ion spectrum to estimate whether a second fragment ion spectrum of the same peptide should be acquired under extended or changed fragmentation conditions.
  • the analysis of the fragment ion spectrum investigates if a dominant ion species occurs in this spectrum.
  • step 200 the various embodiments of this method of acquiring daughter ion spectra of peptide ions in an ion trap mass spectrometer proceed according to the basic pattern illustrated in FIG. 2 .
  • This process begins in step 200 and proceeds to step 202 where the ion trap is filled with ions as supplied by the ion source, and a normal mass spectrum is acquired.
  • step 204 the acquired mass spectrum, which is available in digital form in the memory of the mass spectrometer, is analyzed mathematically by a computer program, and a species of parent ion from which a daughter ion spectrum is to be measured is selected in the usual way according to predefined rules.
  • step 206 the ion trap is again filled with ions, and the selected species of parent ion is isolated in the ion trap in the usual way by ejecting all other ion species.
  • step 208 the ions of this selected species of parent ion are now fragmented in the ion trap, creating fragment ions and, in step 210 a daughter ion spectrum of the fragment ions is measured. Then, in step 212 , the daughter ion spectrum, which is present in digital form in the memory of the mass spectrometer, is analyzed for the occurrence of a dominant ion species.
  • step 214 a determination is made whether a dominant ion species is present. Is no dominant ion species is present, then the process ends in step 216 . However, if, in step 214 , it is determined that a dominant ion species is present, then the process proceeds to step 218 where the ion trap is again filled with ions, and the selected species of parent ion is isolated in the ion trap in the usual way by ejecting all other ion species. In step 220 , the ions of this selected species of parent ion are now fragmented in the ion trap, creating fragment ions. In step 222 , the dominant ion species is fragmented, for example, by resonant excitation and, in step 224 , a daughter ion spectrum of the fragment ions is measured. The process then ends in step 216 .
  • a first favorable embodiment of this basic pattern uses the normal collisionally induced fragmentation that is incorporated as a software-controlled process in every ion trap mass spectrometer, as the mode of fragmentation for the peptide ions in step 208 .
  • this collisionally induced fragmentation frequently only produces daughter ion spectra which mainly comprise one dominant ion species with very few, usually low-intensity, additional ion species. These latter additional ion species of low intensity can often scarcely be evaluated because of poor signal-to-noise ratios.
  • the reason for the occurrence of the dominant ion species is the loss of the modification group in the form of a neutral fragment, and the fast cooling of the residual peptide ion.
  • the modification groups are frequently bound with lower binding energy than the bonds along the chain of amino acids, and they therefore break off very easily.
  • the dominant ion species thus consists here of the residual peptide ions after the modification group was lost from the parent ions.
  • the loss of a neutral modification group can be identified by the fact that the dominant ion species carries the same number of charges per ion as the parent ions. The masses of frequently lost modification groups may corroborate such a neutral loss. If the doubly charged parent ions are selected as parent ions for a favorable collisionally induced fragmentation, then the ions of the dominant ion species present are also doubly charged. If no more modification groups are now present, a collisionally induced fragmentation of this dominant ion species will result in a daughter ion spectrum which has a high information content.
  • the fragmentation of an ion species from a daughter ion spectrum is generally undertaken by acquiring a granddaughter ion spectrum in a process known as MS/MS/MS.
  • the ion trap is first filled with ions, the parent ions are then isolated and fragmented, the species of daughter ion to be analyzed further is then isolated and fragmented, and finally its fragment ions are measured as a granddaughter ion spectrum.
  • This type of process is incorporated as standard in many ion trap mass spectrometers. This process is time-consuming, however.
  • further isolation of the dominant ion species is not necessary, so that a complete MS/MS/MS method does not have to be carried out here.
  • step 218 the same species of parent ion with the same number of charges per ion, i.e. preferably doubly charged, should be selected for this purpose for the repeat measurement.
  • the dominant ion species thus created is then immediately subjected to a further collisionally induced fragmentation in step 222 without first isolating the dominant ion species.
  • the fragmentation of these residual peptide ions can qualitatively improve the daughter ion spectrum and produce a spectrum which can be evaluated, but this improvement does not always occur to the desired extent.
  • FIG. 1B illustrates such a fragment ion spectrum of a dominant ion species, but here the quality is still not sufficient.
  • the quasi granddaughter ion spectrum created in this way can again consist of a dominant ion species.
  • steps 214 - 224 of the method can be repeated as indicated by the dotted arrow 226 with further fragmentation of this now dominant ion species.
  • the masses of the neutral losses may indicate whether it is worthwhile to continue with this process.
  • the analysis of the daughter ion spectrum may also show that a dominant ion species is indeed present, but carries one charge per ion less than the parent ions. What occurs here is the splitting off of an easily removed cation. This loss of a cation generally occurs when the peptide ion is complexed with an alkali ion. Frequently the ions which split off are sodium ions (23 atomic mass units), potassium ions (39 mass units) or ammonium ions (18 mass units); but more complex cations also get lost.
  • the species of parent ion selected at step 218 for the repeat measurement should, if possible, carry one charge per ion more than the previously measured species of parent ion selected in step 204 so that the second fragmentation is carried out on a multiply charged ion species.
  • a second favorable embodiment of the method requires an ion trap mass spectrometer which is equipped with a device for electron-induced fragmentation.
  • This device can contain an ion source to generate negative reactant ions which, after isolation of the parent ions, are filled into the ion trap, where they react with the positively charged parent ions, giving up electrons to form fragment ions.
  • the device can contain a source for highly excited neutral atoms, for example a fast atom bombardment source (FAB), which supplies highly excited, but well-focused, helium atoms, with which the isolated parent ions can be bombarded in the ion trap, triggering electron-induced fragmentation (MAID) by transfer of an electron.
  • FAB fast atom bombardment source
  • the controls of the measurement procedures in the ion trap which are necessary for this method are familiar to those skilled in the art. They are implemented in the control software for the ion trap mass spectrometer.
  • Modern types of liquid chromatography provide the directly coupled mass spectrometer with each of the separated peptides for around five to twenty seconds. An analyte substance is therefore available for measuring for several seconds.
  • Modern ion trap mass spectrometers which can acquire several fragment ion spectra per second, are therefore able to remeasure fragment ion spectra which are promising but not good enough.
  • Such mass spectrometers which have both collisionally induced as well as electron-induced fragmentation available to them, are then able to mathematically analyze the daughter ion spectra at precisely the time when the other mode of fragmentation is being applied to the parent ions. This means that practically unlimited time is available for a careful evaluation.
  • the separation method does not necessarily have to be coupled directly with the mass spectrometry, in order to benefit from the present invention.
  • a measurement procedure which is being used more and more frequently is the non-direct coupling of liquid chromatography with a mass spectrometer which ionizes solid samples on a sample support with matrix-assisted laser desorption (“LC MALDI”).
  • LC MALDI matrix-assisted laser desorption
  • the eluate from the liquid chromatograph is put, in the form of many individual droplets, onto previously prepared sample supports, which can accommodate hundreds or even thousands of samples.
  • the sample droplets are dried and then fed to the mass spectrometer.
  • the invention presented here can only be used properly for LC-MALDI if multiply charged ions are successfully generated which are more favorable for a fragmentation than singly charged ones.

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080054173A1 (en) * 2006-09-04 2008-03-06 Hitachi High-Technologies Corporation Ion trap mass spectrometry method
US20130240723A1 (en) * 2010-11-08 2013-09-19 Dh Technologies Development Pte. Ltd. Systems and Methods for Rapidly Screening Samples by Mass Spectrometry
US20150060657A1 (en) * 2012-04-05 2015-03-05 The University Of British Columbia MS/MS Analysis Using ECD or ETD Fragmentation
US20150214020A1 (en) * 2014-01-29 2015-07-30 Bruker Daltonik Gmbh Acquisition of fragment ion mass spectra of biopolymers in mixtures
US9881778B2 (en) 2014-04-17 2018-01-30 Micromass Uk Limited Hybrid acquisition method incorporating multiple dissociation techniques
US20220093378A1 (en) * 2020-09-21 2022-03-24 Thermo Finnigan Llc Using real time search results to dynamically exclude product ions that may be present in the master scan

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005061425B4 (de) * 2005-12-22 2009-06-10 Bruker Daltonik Gmbh Rückgesteuerte Fragmentierung in Ionenfallen-Massenspektrometern
CN101558470B (zh) * 2006-08-25 2011-04-13 塞莫费尼根股份有限公司 在质谱仪中对解离类型的数据依赖的选择
GB0900973D0 (en) * 2009-01-21 2009-03-04 Micromass Ltd Method and apparatus for performing MS^N
US8153961B2 (en) * 2009-08-31 2012-04-10 Thermo Finnigan Llc Methods for acquisition and deductive analysis of mixed fragment peptide mass spectra
US8455818B2 (en) 2010-04-14 2013-06-04 Wisconsin Alumni Research Foundation Mass spectrometry data acquisition mode for obtaining more reliable protein quantitation
GB201406981D0 (en) * 2014-04-17 2014-06-04 Micromass Ltd Hybrid acquisition method incorporating electron transfer dissociation triggered from fast sequential 2D MS/MS collision induced dissociation
JP2023502923A (ja) * 2019-11-14 2023-01-26 ディーエイチ テクノロジーズ デベロップメント プライベート リミテッド 質量分析の方法－直交断片化方法論を用いたｓｗａｔｈ

Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4736101A (en) 1985-05-24 1988-04-05 Finnigan Corporation Method of operating ion trap detector in MS/MS mode
US5171991A (en) * 1991-01-25 1992-12-15 Finnigan Corporation Quadrupole ion trap mass spectrometer having two axial modulation excitation input frequencies and method of parent and neutral loss scanning
EP0898297A2 (de) 1997-08-22 1999-02-24 Micromass Limited Verfahren und Vorrichtung zur Tandem-Massenspektrometrie
US5903003A (en) * 1997-03-06 1999-05-11 Bruker Daltonik Gmbh Methods of comparative analysis using ion trap mass spectrometers
WO1999038193A1 (en) 1998-01-23 1999-07-29 Analytica Of Branford, Inc. Mass spectrometry with multipole ion guide
US5936241A (en) * 1997-03-06 1999-08-10 Bruker Daltonik Gmbh Method for space-charge control of daughter ions in ion traps
EP0786796B1 (de) 1992-05-29 2000-07-05 Varian, Inc. Verfahren zum Betrieb von Ionenfallenmassenspektrometern
US6410913B1 (en) * 1999-07-14 2002-06-25 Bruker Daltonik Gmbh Fragmentation in quadrupole ion trap mass spectrometers
US20020175280A1 (en) * 2000-11-25 2002-11-28 Bruker Daltonik Gmbh Ion fragmentation by electron capture in high-frequency ion traps
US20030077616A1 (en) * 2001-04-19 2003-04-24 Ciphergen Biosystems, Inc. Biomolecule characterization using mass spectrometry and affinity tags
US6559444B2 (en) * 2000-03-07 2003-05-06 Bruker Daltonik Gmbh Tandem mass spectrometer comprising only two quadrupole filters
US6753523B1 (en) * 1998-01-23 2004-06-22 Analytica Of Branford, Inc. Mass spectrometry with multipole ion guides
US20050048564A1 (en) * 2001-05-30 2005-03-03 Andrew Emili Protein expression profile database
US6888130B1 (en) * 2002-05-30 2005-05-03 Marc Gonin Electrostatic ion trap mass spectrometers
US6924478B1 (en) * 2004-05-18 2005-08-02 Bruker Daltonik Gmbh Tandem mass spectrometry method
US20050221500A1 (en) * 2002-05-20 2005-10-06 Purdue Research Foundation Protein identification from protein product ion spectra
US6977370B1 (en) * 2003-04-07 2005-12-20 Ciphergen Biosystems, Inc. Off-resonance mid-IR laser desorption ionization
US20060186331A1 (en) * 2005-01-31 2006-08-24 Bruker Daltonik Gmbh Ion fragmentation by electron transfer in ion traps
US20060289738A1 (en) * 2005-06-03 2006-12-28 Bruker Daltonik Gmbh Measurement of light fragment ions with ion traps
US20070084998A1 (en) * 2005-08-22 2007-04-19 Bruker Daltonik Gmbh Novel tandem mass spectrometer
US20070158544A1 (en) * 2005-12-22 2007-07-12 Bruker Daltonik Gmbh Feedback fragmentation in ion trap mass spectrometers
US7276688B2 (en) * 2004-03-25 2007-10-02 Bruker Daltonik Gmbh Ion-optical phase volume compression
US20080093547A1 (en) * 2006-10-24 2008-04-24 Bruker Daltonik Gmbh Top-down protein analysis in mass spectrometers with ion traps
US20080135747A1 (en) * 2006-12-04 2008-06-12 Bruker Daltonik Gmbh Collision-induced decomposition of ions in rf ion traps

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0575777B1 (de) * 1992-05-29 1998-09-23 Varian Associates, Inc. Verfahren zur Verwendung eines Massenspektrometers

Patent Citations (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4736101A (en) 1985-05-24 1988-04-05 Finnigan Corporation Method of operating ion trap detector in MS/MS mode
US5171991A (en) * 1991-01-25 1992-12-15 Finnigan Corporation Quadrupole ion trap mass spectrometer having two axial modulation excitation input frequencies and method of parent and neutral loss scanning
EP0786796B1 (de) 1992-05-29 2000-07-05 Varian, Inc. Verfahren zum Betrieb von Ionenfallenmassenspektrometern
US5903003A (en) * 1997-03-06 1999-05-11 Bruker Daltonik Gmbh Methods of comparative analysis using ion trap mass spectrometers
US5936241A (en) * 1997-03-06 1999-08-10 Bruker Daltonik Gmbh Method for space-charge control of daughter ions in ion traps
EP0898297A2 (de) 1997-08-22 1999-02-24 Micromass Limited Verfahren und Vorrichtung zur Tandem-Massenspektrometrie
US6753523B1 (en) * 1998-01-23 2004-06-22 Analytica Of Branford, Inc. Mass spectrometry with multipole ion guides
WO1999038193A1 (en) 1998-01-23 1999-07-29 Analytica Of Branford, Inc. Mass spectrometry with multipole ion guide
US6410913B1 (en) * 1999-07-14 2002-06-25 Bruker Daltonik Gmbh Fragmentation in quadrupole ion trap mass spectrometers
US6559444B2 (en) * 2000-03-07 2003-05-06 Bruker Daltonik Gmbh Tandem mass spectrometer comprising only two quadrupole filters
US20020175280A1 (en) * 2000-11-25 2002-11-28 Bruker Daltonik Gmbh Ion fragmentation by electron capture in high-frequency ion traps
US6653622B2 (en) * 2000-11-25 2003-11-25 Bruker Daltonik Gmbh Ion fragmentation by electron capture in high-frequency ion traps
US20030077616A1 (en) * 2001-04-19 2003-04-24 Ciphergen Biosystems, Inc. Biomolecule characterization using mass spectrometry and affinity tags
US20050048564A1 (en) * 2001-05-30 2005-03-03 Andrew Emili Protein expression profile database
US20050221500A1 (en) * 2002-05-20 2005-10-06 Purdue Research Foundation Protein identification from protein product ion spectra
US6888130B1 (en) * 2002-05-30 2005-05-03 Marc Gonin Electrostatic ion trap mass spectrometers
US6977370B1 (en) * 2003-04-07 2005-12-20 Ciphergen Biosystems, Inc. Off-resonance mid-IR laser desorption ionization
US7276688B2 (en) * 2004-03-25 2007-10-02 Bruker Daltonik Gmbh Ion-optical phase volume compression
US6924478B1 (en) * 2004-05-18 2005-08-02 Bruker Daltonik Gmbh Tandem mass spectrometry method
US20060186331A1 (en) * 2005-01-31 2006-08-24 Bruker Daltonik Gmbh Ion fragmentation by electron transfer in ion traps
US7456397B2 (en) * 2005-01-31 2008-11-25 Bruker Daltonik Gmbh Ion fragmentation by electron transfer in ion traps
US20060289738A1 (en) * 2005-06-03 2006-12-28 Bruker Daltonik Gmbh Measurement of light fragment ions with ion traps
US20070084998A1 (en) * 2005-08-22 2007-04-19 Bruker Daltonik Gmbh Novel tandem mass spectrometer
US20070158544A1 (en) * 2005-12-22 2007-07-12 Bruker Daltonik Gmbh Feedback fragmentation in ion trap mass spectrometers
US20080093547A1 (en) * 2006-10-24 2008-04-24 Bruker Daltonik Gmbh Top-down protein analysis in mass spectrometers with ion traps
US20080135747A1 (en) * 2006-12-04 2008-06-12 Bruker Daltonik Gmbh Collision-induced decomposition of ions in rf ion traps

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080054173A1 (en) * 2006-09-04 2008-03-06 Hitachi High-Technologies Corporation Ion trap mass spectrometry method
US7989764B2 (en) * 2006-09-04 2011-08-02 Hitachi High-Technologies Corporation Ion trap mass spectrometry method
US20130240723A1 (en) * 2010-11-08 2013-09-19 Dh Technologies Development Pte. Ltd. Systems and Methods for Rapidly Screening Samples by Mass Spectrometry
US9269553B2 (en) * 2010-11-08 2016-02-23 Dh Technologies Development Pte. Ltd. Systems and methods for rapidly screening samples by mass spectrometry
US9543134B2 (en) 2010-11-08 2017-01-10 Dh Technologies Development Pte. Ltd. Systems and methods for rapidly screening samples by mass spectrometry
US20150060657A1 (en) * 2012-04-05 2015-03-05 The University Of British Columbia MS/MS Analysis Using ECD or ETD Fragmentation
US9129783B2 (en) * 2012-04-05 2015-09-08 Micromass Uk Limited MS/MS analysis using ECD or ETD fragmentation
US20150214020A1 (en) * 2014-01-29 2015-07-30 Bruker Daltonik Gmbh Acquisition of fragment ion mass spectra of biopolymers in mixtures
US9595427B2 (en) * 2014-01-29 2017-03-14 Bruker Daltonik Gmbh Acquisition of fragment ion mass spectra of biopolymers in mixtures
US9881778B2 (en) 2014-04-17 2018-01-30 Micromass Uk Limited Hybrid acquisition method incorporating multiple dissociation techniques
US20220093378A1 (en) * 2020-09-21 2022-03-24 Thermo Finnigan Llc Using real time search results to dynamically exclude product ions that may be present in the master scan
US11587774B2 (en) * 2020-09-21 2023-02-21 Thermo Finnigan Llc Using real time search results to dynamically exclude product ions that may be present in the master scan

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GB2436437A (en) 2007-09-26
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